SITC Leaders Weigh in on New Research Published in Nature

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Studies Find Potentially Predictive Biomarkers May Lead to Better Patient Outcomes, Bladder Cancer Treatment Options Extend Beyond Chemotherapy

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Being able to select patients whose immune system is ready to attack the cancer, but is being held back by PD-1, could be one of the main factors in determining the appropriate treatment for many patients with advanced cancers.

Leaders from the Society for Immunotherapy of Cancer (SITC) are weighing in on new developments in cancer research that were recently published in Nature.

Patient adherence has long been a challenge for clinicians when selecting treatment approaches for their patients. Now, with the help of predictive biomarkers, doctors have a better way of qualifying patients for specific treatment methods that lead to improved patient outcomes. Among the predictive biomarkers is the presence of tumor-infiltrating CD8+T cells, or “killer T cells.” Under certain conditions these lymphocytes are capable of killing cancer cells, cells infected with viruses, or cells that are damaged in other ways. One Nature study (http://www.nature.com/nature/journal/v515/n7528/full/nature13954.html#access) revealed that the presence of pre-existing CD8+T cells localized at the tumor margin was required for positive immune response in patients treated with pembrolizumab, an anti-PD-1 therapy.

According to physician-scientist Antoni Ribas, MD, PhD, “Being able to select patients whose immune system is ready to attack the cancer, but is being held back by PD-1, could be one of the main factors in determining the appropriate treatment for many patients with advanced cancers.” For patients with advanced melanoma, this means that the tumor presence of CD8+T cells will be a critical factor in determining whether to treat with pembrolizumab. Those without these T cells already present in their tumors will be able to seek more viable treatment options from the onset.

PD-1 (programmed cell death-1) receptor sends negative signals to the T cell when it is engaged to either of its natural ligands, PD-L1 or PD-L2. These negative signals normally slow or completely shut down the immune response when it is no longer necessary. Certain cancer cells have the ability to influence the engagement of this checkpoint receptor, which puts the brakes on the immune response. Anti-PD-1 and anti-PD-L1 directed therapies release the brakes, allowing the immune system to restore function and attack the cancer cells.

“The articles published in Nature (http://www.nature.com) give us a more complete picture of how immunotherapy treatment impacting PD-1 and PDL-1 works,” explained physician-scientist and SITC Board member Jedd Wolchok, MD, PhD. Because of this understanding, researchers have been able to apply anti-PD-1 and anti-PDL-1 therapies and generate initial promising results in cancers not previously thought to be amenable for immunotherapy.

Wolchok pointed out that the “most significant clinical development [resulting from the latest research] is that bladder cancer is now on the list of cancers that can be treated with immunotherapy” (http://www.nature.com/nature/journal/v515/n7528/full/nature13904.html). Bladder cancer survival rates have historically been low, with no advances in treatment options for the last 30 years. Chemotherapy, the traditional treatment method for this type of cancer, has proven ineffective or intolerable for many. Immunotherapy may be a more viable, tolerable approach especially for older patients.

Immunotherapy, an innovative type of cancer treatment that harnesses the power of the body’s own immune system to fight cancer, has long been a focus for many researchers due to its potential for high efficacy and low toxicity by activating immune cells and allowing them to identifying and destroying cancer cells while keeping healthy cells intact. This new generation of checkpoint inhibitors (anti-PD-1 and anti-PDL-1) are less likely to affect healthy tissues and cells, meaning side effects may be less common and either less severe or more easily treatable than those associated with “standard cancer treatments” such as: chemotherapy, radiation, and surgery.

Today, as the leading cancer immunotherapy organization, SITC is witnessing and championing the accelerated development of the immunotherapy field for the treatment of numerous malignancies. “The recent publication of several papers dealing with various aspects of tumor immunotherapy in Nature highlight the progress and promise of this approach for the treatment of cancer,” explained SITC President Howard Kaufman, MD, FACS. “A better understanding of how the immune system recognizes and eradicates cancer is providing new opportunities for clinical intervention and identification of predictive biomarkers.”

About SITC
Founded in 1984, Society for Immunotherapy of Cancer (SITC) is a non-profit medical society dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy through the core values of interaction, innovation and leadership. For more information on SITC, visit the Society website at: http://www.sitcancer.org.

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